Skin whitening external preparation

ABSTRACT

The invention relates to skin whitening external preparations which contain tocopherol phosphate and/or a salt thereof as an active ingredient capable of prevention and/or removal of skin pigmentation, cosmetics including the skin whitening external preparation and cosmetic cares using the cosmetic. The skin whitening external preparations have excellent skin whitening effects and are readily producible so that they can find wide use for the purpose of skin whitening.

CROSS REFERENCE OF RELATED APPLICATION

This application is an application filed under 35 U.S.C. §111 (a)claiming benefit pursuant to 35 U.S.C. §119 (e) (1) of the filing dateof Provisional Application 60/379,753 filed on May 14, 2002 pursuant to35 U.S.C. §111 (b).

TECHNICAL FIELD

The present invention relates to skin whitening external preparationswhich contain tocopherol phosphate and/or a salt thereof as an activeingredient capable of prevention and/or removal of pigmentation,cosmetics comprising the skin whitening external preparation andcosmetic cares using the cosmetic.

BACKGROUND ART

Many external preparations have been developed for use to treat skinpigmentation, such as spots or freckles by exposure to ultraviolet rays,wounds, burn scars and darkening of surgical scars.

For example, polyphenols are widely known to have depigmentation effectsby reducing melanin pigments, and hydroquinones in particular have beenclinically used quite often in U.S. and other countries. However, it hasbeen pointed out that the compound causes strong irritation on skin andis hardly a safe drug for skin which can be used without anxiety.

Cosmetics often contain vitamin C or a derivative thereof, such asascorbic acid 2-phosphate or ascorbic acid 2-glucoside, as a whiteningagent. It has been confirmed that oral administration of tocopherols iseffective against pigmentation (K. Werininghaus et al., Arch Dermatol,130, 1257, 1997). Also, effects of suppressed pigmentation by a specificderivative, tocopherol ferulate, have been confirmed with cultured cells(M. Ichihashi et al., Anticancer Res., 19, 3769, 1999). However, therehas been no report on successful prevention or removal of pigmentationby percutaneous administration of tocopherol.

Tocopherols knows as vitamin E (e.g., α-tocopherol, β-tocopherol,γ-tocopherol and δ-tocopherol) and derivatives, such as tocopherolacetate and tocopherol nicotinate, have been used in medical drugs,cosmetics and feeds on account of their effects of antioxidation,biomembrane stabilization, immune activation and facilitation of bloodcirculation.

These tocopherol derivatives are oil soluble to cause difficulties inmaking preparations, so that water-soluble tocopherol phosphates, aminoacid esters and alkylaminocarboxylates have been proposed.

However, there has been no report on anti-pigmentation agents whichcomprise any of the tocopherols inclusive of the tocopherol phosphates.

DISCLOSURE OF THE INVENTION

It is an object of the invention to provide highly safe and readilyproducible skin whitening agents excellent in prevention and/or removalof pigmentation, and particularly cosmetics of excellent whiteningability and cosmetic cares using the cosmetic.

As a result of earnest studies to solve the above problems, the presentinventors have found that skin whitening external preparations thatcomprise tocopherol phosphate and/or a salt thereof have high effects ofprevention and removal of pigmentation. The invention has been completedbased on the finding.

The invention relates to:

[1] A skin whitening external preparation which comprises tocopherolphosphate and/or a salt thereof as an active ingredient capable ofprevention and/or removal of skin pigmentation.

[2] The skin whitening external preparation of [1], wherein thetocopherol phosphate is represented by the formula

wherein R₁, R₂ and R₃ are each hydrogen or a methyl group.

[3] The skin whitening external preparation of [1] or [2], wherein thetocopherol phosphate is α-tocopherol phosphate.

[4] The skin whitening external preparation of [3], wherein theα-tocopherol phosphate is dl-α-tocopherol phosphate.

[5] The skin whitening external preparation of [3], wherein theα-tocopherol phosphate is d-α-tocopherol phosphate.

[6] The skin whitening external preparation of [1] or [2], wherein thetocopherol phosphate is γ-tocopherol phosphate.

[7] The skin whitening external preparation of [6], wherein theγ-tocopherol phosphate is d-γ-tocopherol phosphate.

[8] The skin whitening external preparation of [1] or [2], wherein thetocopherol phosphate is δ-tocopherol phosphate.

[9] The skin whitening external preparation of [8], wherein theδ-tocopherol phosphate is d-δ-tocopherol phosphate.

[10] The skin whitening external preparation of any of [1] to [9],wherein the salt of tocopherol phosphate is a sodium salt.

[11] The skin whitening external preparation of any of [1] to [10],wherein the content of the tocopherol phosphate and/or the salt thereofis from 0.1 to 10% by mass.

[12] A cosmetic comprising the skin whitening external preparation ofany of [1] to [11].

[13] The cosmetic of [12], which is in the form of gel, emulsion orlotion.

[14] A cosmetic care using the cosmetic of [12] or [13].

[15] A use of tocopherol phosphate and/or a salt thereof in skinwhitening external preparations as an active ingredient capable ofprevention and/or removal of skin pigmentation.

[16] A skin whitening method comprising percutaneously administratingtocopherol phosphate and/or a salt thereof.

BEST MODE FOR CARRYING OUT THE INVENTION

The effective ingredients, the tocopherol phosphate and the saltthereof, of the invention will be described first.

The tocopherol phosphate is, for example, represented by the formula(1):

wherein R₁, R₂ and R₃ are each hydrogen or a methyl group.

Preferably, and most usually, the tocopherol phosphate is α-tocopherolphosphate in which R₁, R₂ and R₃ are all methyl groups, γ-tocopherolphosphate in which R₁ and R₂ are both methyl groups and R₃ is hydrogen,or δ-tocopherol phosphate in which R₁ is a methyl group and R₂ and R₃are both hydrogen.

Examples of preferred salts of the tocopherol phosphate include sodium,potassium, ammonium, alkylammonium, magnesium, calcium and zinc salts.

Of these, sodium salt is particularly preferable since it has highsolubility in water and is easy to handle owing to its particulatestate.

The tocopherol phosphate of the formula (1) has an asymmetric carbonatom at the second position of the chroman ring, so that the tocopherolphosphate can naturally be a d- or l-stereoisomer or a dl-isomer. Thetocopherol phosphate may be any of these isomers.

The tocopherol phosphate and/or the salt thereof can be obtained by aconventional method, e.g., JP-A-59 (1984)/44375 or WO 97/14705.

Specifically, the objective tocopherol phosphate can be obtained bycausing a phosphorylating agent, such as phosphorous oxychloride, toreact with tocopherol dissolved in a solvent, and appropriatelypurifying the resulting reaction product.

The objective salt of tocopherol phosphate can be obtained byneutralizing the tocopherol phosphate with a metallic oxide, such asmagnesium oxide, a metallic hydroxide, such as sodium hydroxide,ammonium hydroxide or alkylammonium hydroxide.

In the invention, the term “skin whitening” means that the skinwhitening external preparations can prevent and/or remove skinpigmentation by the effects of prevention and/or removal of skinpigmentation by the active ingredients tocopherol phosphate and saltthereof.

The active ingredients, the tocopherol phosphate and the salt thereof,capable of prevention and/or removal of skin pigmentation are used inamounts appropriately controlled depending on the objective whiteningeffects. Preferably, the skin whitening agent contains the tocopherolphosphate and/or the salt thereof in 0.1 to 10% by mass.

For example, the tocopherol phosphate and/or the salt thereof will bedesirably contained in 0.1 to 8% by mass in the case of skin whiteninglotions, and in 0.1 to 10% by mass in the case of skin whitening gels.

The skin whitening external preparations can be used as cosmetics.

The cosmetic cares of the invention in which the skin whitening externalpreparation or the cosmetic is used, are also effective for preventionand/or removal of skin pigmentation.

The cosmetics may be any kind of cosmetics usable in contact with skinand can be employed irrespective of age and sex of user. Examples of thecosmetics include skin milks, skin creams, skin foundations, massagecreams, cleansing creams, shaving creams, cleansing foams, skin toners,lotions, skin packs, shampoos, conditioners, ointments, bath powders andbody soaps.

The skin whitening external preparations may contain other ingredientscommonly used in external preparations for skin within limits notdetrimental to the effects of the invention. Exemplary ingredients arethose listed in The Japanese Standards of Cosmetic Ingredients 2ndedition (edited by Society of Japanese Pharmacopoeia and published byYakuji Nippo, Ltd. (1984)), The Japanese Cosmetic Ingredients Codex(edited by Ministry of Health and Welfare, Pharmaceutical ExaminationDivision and published by Yakuji Nippo, Ltd. (1993)), Supplement to TheJapanese Cosmetic Ingredients Codex (edited by Ministry of Health andWelfare, Pharmaceutical Examination Division and published by YakujiNippo, Ltd. (1993)), The Comprehensive Licensing Standards of Cosmeticsby Category (edited by Ministry of Health and Welfare, PharmaceuticalExamination Division and published by Yakuji Nippo, Ltd. (1993)) andDictionary of Cosmetic Ingredients (Nikko Chemicals., Co. Ltd. (1991)).Of these ingredients, the skin whitening preparations can achieveparticularly enhanced skin whitening effects by additionally containinga known skin whitening ingredient ascorbic acid or a derivative thereof,such as magnesium ascorbyl 2-phosphate, sodium ascorbyl 2-phosphate,ascorbyl glucoside, sodium ascorbyl 2-phosphoric acid-6-palmitate,sodium ascorbyl 2-phosphoric acid-6-hexyl decanoate, ascorbyltetraisopalmitate or 3-0-ethyl ascorbate. The above additionalingredients may be contained in amounts within 0.1 to 10%. Other skinwhitening ingredients, such as arbutin, ellagic acid, kojic acid,chamomile extract and Rucinol, may by used in combination.

For the purpose of cosmetic care, the cosmetics are preferably in theform of, although not particularly limited to, gel, emulsion or liquid,such as gel emulsions, cosmetic liquids and lotions. Compositions of theemulsions, cosmetic liquids, etc. are not specifically limited and canbe in accordance with commonly allied formulations.

EXAMPLES

The present invention will be described in greater detail by thefollowing Examples, but it should be construed that the invention is inno way limited to those Examples.

In the Examples, the concentrations are in mass percentage.

Synthetic Example

dl-α-Tocopherol 25.0 g (0.05 mol) was dissolved in toluene 75 ml whichcontained pyridine 9.3 g. Phosphorous oxychloride 9.8 g (0.064 mol) wasdropwise added to the solution with stirring at room temperature (about15° C.) to 50° C., and reaction was further conducted at roomtemperature for 3 hours. The precipitated salt was dissolved by additionof 100 ml of a 10% aqueous solution of sulfuric acid, and the organicphase and the aqueous phase were separated. 100 ml of a 10% aqueoussolution of sulfuric acid was added to the organic phase, and themixture was heated under reflux for 4 hours. Then the organic phase wasseparated, washed with a 5% aqueous solution of sulfuric acid andconcentrated to dryness by evaporation to obtain dl-α-tocopherolphosphate.

The dl-α-tocopherol phosphate was dissolved in an alcohol, and theresulting solution was neutralized with a methanol solution of sodiumhydroxide. The neutralized solution was added to a methanol-acetonesolvent to reprecipitate sodium dl-α-tocopherol phosphate, which wasthereafter obtained as white powder.

Corresponding sodium salts of tocopherol phosphate were obtained usingd-α-tocopherol, d-γ-tocopherol and d-δ-tocopherol in place ofdl-α-tocopherol.

Example 1

Lotion 1

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1)dl-α-tocopherol phosphate 2.0 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 2

Lotion 2

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumdl-α-tocopherol phosphate 2.0 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 3

Lotion 3

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumd-α-tocopherol phosphate 2.0 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 4

Lotion 4

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumd-γ-tocopherol phosphate 2.0 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 5

Lotion 5

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumd-δ-tocopherol phosphate 2.0 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Comparative Example 1

Lotion 6

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that a lotion containing a commonly used whiteningingredient sodium ascorbyl 2-phosphate, was obtained. 1) sodium ascorbyl2-phosphate 2.0 2) ethanol 5.0 3) propylene glycol 5.0 4) methylparahydroxybenzoate 0.2 5) purified water residue

Comparative Example 2

Lotion 7

A homogeneous dispersion-solution consisting of the ingredients 1) to 3)was added to the ingredient 4) with stirring in the following finalconcentrations, so that a lotion containing no whitening ingredient wasobtained. 1) ethanol 5.0 2) propylene glycol 5.0 3) methylparahydroxybenzoate 0.2 4) purified water residue

All the lotions obtained as above were homogeneous solutions that hadexcellent storage stability.

Example 6

Lotion 8

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1)dl-α-tocopherol phosphate 0.1 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 7

Lotion 9

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumdl-α-tocopherol phosphate 0.1 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 8

Lotion 10

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumd-α-tocopherol phosphate 0.1 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 9

Lotion 11

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumd-γ-tocopherol phosphate 0.1 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Example 10

Lotion 12

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that an objective lotion was obtained. 1) sodiumd-δ-tocopherol phosphate 0.1 2) ethanol 5.0 3) propylene glycol 5.0 4)methyl parahydroxybenzoate 0.2 5) purified water residue

Comparative Example 3

Lotion 13

A homogeneous dispersion-solution consisting of the ingredients 1) to 4)was added to the ingredient 5) with stirring in the following finalconcentrations, so that a lotion containing a commonly used whiteningingredient sodium ascorbyl 2-phosphate, was obtained. 1) sodium ascorbyl2-phosphate 0.1 2) ethanol 5.0 3) propylene glycol 5.0 4) methylparahydroxybenzoate 0.2 5) purified water residue

All the lotions obtained as above were homogeneous solutions that hadexcellent storage stability.

Example 11

External gel 1

A homogeneous dispersion of the ingredient 1) in the ingredient 2) wasadded to the ingredient 3) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium dl-α-tocopherol phosphate 10 2) glycerol 20 3) octyldodecylmyristate 70

Example 12

External gel 2

A homogeneous dispersion of the ingredient 1) in the ingredient 2) wasadded to the ingredient 3) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium d-α-tocopherol phosphate 10 2) glycerol 20 3) octyldodecylmyristate 70

Example 13

External gel 3

A homogeneous dispersion of the ingredient 1) in the ingredient 2) wasadded to the ingredient 3) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium d-γ-tocopherol phosphate 10 2) glycerol 20 3) octyldodecylmyristate 70

Example 14

External gel 4

A homogeneous dispersion of the ingredient 1) in the ingredient 2) wasadded to the ingredient 3) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium d-δ-tocopherol phosphate 10 2) glycerol 20 3) octyldodecylmyristate 70

Comparative Example 4

External gel 5

A homogeneous dispersion of the ingredient 1) in the ingredient 2) wasadded to the ingredient 3) with stirring in the following finalconcentrations, so that an external gel containing a commonly usedwhitening ingredient sodium ascorbyl 2-phosphate, was obtained. 1)sodium ascorbyl 2-phosphate 10 2) glycerol 20 3) octyldodecyl myristate70

Comparative Example 5

External gel 6

The ingredient 1) was added to the ingredient 2) with stirring, and theingredient 3) was added to the mixture, so that an external gelcontaining no whitening ingredient was obtained. 1) glycerol 20 2)octyldodecyl myristate 70 3) purified water 10

All the external gels obtained as above were homogeneous dispersionsthat had excellent storage stability.

(Measurement of Preventive Effects for Pigmentation)

Fifty male guinea pigs (7 weeks old, weiser maple species, SPF) wereshorn on their entire backs with electric clippers (0.05 mm blade) andthereafter shaven with an electric shaver. The exposed skin was coveredwith an adhesive stretch bandage (SILKYTEX, overlaid with aluminum foilon outer surface) which had six windows 1.5 cm×1.5 cm.

Each of the lotions 1-13 and the external gels 1-6 obtained in theExamples 1-14 and the Comparative Examples 1-5, was sequentially appliedto 10 window openings in an amount of 0.05 ml per site.

Four hours later, the treated sites were washed with wet absorbentcotton and dried. Then the every guinea pig was secured in a retainingapparatus and exposed to ultraviolet beams (UVB) of medium wavelength bymeans of an ultraviolet irradiation device (product of ShinanoSeisakusho, provided with fluorescent lamps FL 40S/E30 (TOSHIBA LIGHTING& TECHNOLOGY CORPORATION) and six SE lamps), so that the open sites wereirradiated with ultraviolet rays in 300 mJ/cm² dose at a distance ofabout 10 cm.

The irradiation was followed by application of the same lotions 1-13 andthe same external gels 1-6 to the same corresponding sites in an amountof 0.05 ml. This procedure was repeatedly carried out for 3 days. After28 days from the final irradiation, the pigmentation degree wasevaluated by marks for each site according to the following criteria.Also, the brightness of skin color was measured with a color differencemeter (CR-20 available from MINOLTA Co., Ltd.) at five points: the fourcorners and the center point of the treated/irradiated site.

Preventive effects for pigmentation were judged based on the averagevalues of the marks (for the 10 sites) and of the brightness (for the 50points) of the preparation. Criteria for judgment of pigmentation degreeno pigmentation 0 slight pigmentation 1 mild pigmentation 2 moderatepigmentation 3 severe pigmentation 4 Result (average value) PreparationAverage Mark Brightness Lotion 1 1.2 64.5 Lotion 2 1.2 64.7 Lotion 3 1.064.7 Lotion 4 1.4 64.2 Lotion 5 1.4 64.7 Lotion 6 1.4 64.6 Lotion 7 3.261.9 Lotion 8 2.6 63.1 Lotion 9 2.4 62.8 Lotion 10 2.2 63.3 Lotion 112.4 62.3 Lotion 12 2.6 62.6 Lotion 13 2.8 62.7 External gel 1 0.4 66.0External gel 2 0.2 65.6 External gel 3 0.2 66.3 External gel 4 0.6 66.9External gel 5 0.6 65.8 External gel 6 3.4 61.0

The above results confirmed excellent pigmentation preventive effects ofthe present lotions and external gels comparable to those of the commonwhitening ingredient sodium ascorbyl 2-phosphate.

(Measurement of Removal Effects for Pigmentation)

Fifty male guinea pigs (6 weeks old, weiser maple species, SPF) wereshorn on their entire backs with electric clippers (0.05 mm blade) andthereafter shaven with an electric shaver. The exposed skin was coveredwith an adhesive stretch bandage (SILKYTEX, overlaid with aluminum foilon outer surface) which had six windows 1.5 cm×1.5 cm. Then the everyguinea pig was secured in a retaining apparatus and exposed toultraviolet beams (UVB) of medium wavelength by means of an ultravioletirradiation device (product of Shinano Seisakusho, provided withfluorescent lamps FL 40S/E30 (TOSHIBA LIGHTING & TECHNOLOGY CORPORATION)and six SE lamps), so that the open sites were irradiated withultraviolet rays in 750 mJ/cm² dose at a distance of about 10 cm.

Over the period from the 4th day to the 28th day counted from the finalirradiation, each of the lotions 1-13 and the external gels 1-6 obtainedin the Examples 1-14 and the Comparative Examples 1-5, was sequentiallyapplied to 10 window openings in an amount of 0.05 ml per site twice aday in the morning and the evening.

On the 28th day, the pigmentation degree was evaluated by marks for eachsite according to the same criteria as in the measurement of preventiveeffects for pigmentation.

Removal effects for pigmentation were judged based on the average valueof the marks (for the 10 sites) of the preparation. Result (averagevalue) Preparation Average Mark Lotion 1 1.8 Lotion 2 1.8 Lotion 3 1.6Lotion 4 1.8 Lotion 5 1.6 Lotion 6 1.8 Lotion 7 3.4 Lotion 8 2.6 Lotion9 2.4 Lotion 10 2.2 Lotion 11 2.4 Lotion 12 2.6 Lotion 13 2.6 Externalgel 1 1.6 External gel 2 1.8 External gel 3 1.6 External gel 4 1.6External gel 5 1.4 External gel 6 3.6

The above results confirmed remarkable pigmentation removal effects ofthe present lotions and external gels comparable to those of the commonwhitening ingredient sodium ascorbyl 2-phosphate.

Example 15

Further, lotions, emulsions and external gels were prepared with thefollowing formulations.

Lotion 14

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectivelotion was obtained. 1) sodium dl-α-tocopherol phosphate 0.1 2) ethanol5.0 3) propylene glycol 5.0 4) methyl parahydroxybenzoate 0.2 5) sodiumascorbyl 2-phosphate 3.0 6) purified water residueLotion 15

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectivelotion was obtained. 1) sodium d-α-tocopherol phosphate 0.1 2) ethanol5.0 3) propylene glycol 5.0 4) methyl parahydroxybenzoate 0.2 5) sodiumascorbyl 2-phosphate 3.0 6) purified water residueLotion 16

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectivelotion was obtained. 1) sodium d-γ-tocopherol phosphate 0.1 2) ethanol5.0 3) propylene glycol 5.0 4) methyl parahydroxybenzoate 0.2 5) sodiumascorbyl 2-phosphate 3.0 6) purified water residueLotion 17

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectivelotion was obtained. 1) sodium dl-α-tocopherol phosphate 0.1 2) ethanol5.0 3) propylene glycol 5.0 4) methyl parahydroxybenzoate 0.2 5)magnesium ascorbyl 2-phosphate 3.0 6) purified water residueLotion 18

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectivelotion was obtained. 1) sodium d-α-tocopherol phosphate 0.1 2) ethanol5.0 3) propylene glycol 5.0 4) methyl parahydroxybenzoate 0.2 5) sodiumascorbyl 2-phosphate 3.0 6) purified water residueLotion 19

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectivelotion was obtained. 1) sodium d-γ-tocopherol phosphate 0.1 2) ethanol5.0 3) propylene glycol 5.0 4) methyl parahydroxybenzoate 0.2 5)magnesium ascorbyl 2-phosphate 3.0 6) purified water residueEmulsion 1

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectiveemulsion was obtained. 1) sodium dl-α-tocopherol phosphate 1.0 2)hydrogenated soybean phospholipid 10.0 3) triglyceride 2-ethylhexanoate20.0 4) methyl parahydroxybenzoate 0.2 5) sodium ascorbyl 2-phosphate3.0 6) purified water residueEmulsion 2

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectiveemulsion was obtained. 1) sodium d-α-tocopherol phosphate 1.0 2)hydrogenated soybean phospholipid 10.0 3) triglyceride 2-ethylhexanoate20.0 4) methyl parahydroxybenzoate 0.2 5) sodium ascorbyl 2-phosphate3.0 6) purified water residueEmulsion 3

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectiveemulsion was obtained. 1) sodium d-γ-tocopherol phosphate 1.0 2)hydrogenated soybean phospholipid 10.0 3) triglyceride 2-ethylhexanoate20.0 4) methyl parahydroxybenzoate 0.2 5) sodium ascorbyl 2-phosphate3.0 6) purified water residueEmulsion 4

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectiveemulsion was obtained. 1) sodium dl-α-tocopherol phosphate 1.0 2)hydrogenated soybean phospholipid 10.0 3) triglyceride 2-ethylhexanoate20.0 4) methyl parahydroxybenzoate 0.2 5) magnesium ascorbyl 2-phosphate3.0 6) purified water residueEmulsion 5

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectiveemulsion was obtained. 1) sodium d-α-tocopherol phosphate 1.0 2)hydrogenated soybean phospholipid 10.0 3) triglyceride 2-ethylhexanoate20.0 4) methyl parahydroxybenzoate 0.2 5) magnesium ascorbyl 2-phosphate3.0 6) purified water residueEmulsion 6

A homogeneous solution consisting of the ingredients 1) to 4) was addedto the ingredient 6) in which the ingredient 5) had been dissolved withstirring in the following final concentrations, so that an objectiveemulsion was obtained. 1) sodium d-γ-tocopherol phosphate 1.0 2)hydrogenated soybean phospholipid 10.0 3) triglyceride 2-ethylhexanoate20.0 4) methyl parahydroxybenzoate 0.2 5) magnesium ascorbyl 2-phosphate3.0 6) purified water residueExternal Gel 7

A homogeneous solution of the ingredients 1) and 2) in the ingredient 3)was added to the ingredient 4) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium dl-α-tocopherol phosphate 10.0 2) sodium ascorbyl 2-phosphate10.0 3) glycerol 20.0 4) octyldodecyl myristate 60.0External Gel 8

A homogeneous solution of the ingredients 1) and 2) in the ingredient 3)was added to the ingredient 4) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium d-α-tocopherol phosphate 10.0 2) sodium ascorbyl 2-phosphate 10.03) glycerol 20.0 4) octyldodecyl myristate 60.0External Gel 9

A homogeneous solution of the ingredients 1) and 2) in the ingredient 3)was added to the ingredient 4) with stirring in the following finalconcentrations, so that an objective external gel was obtained. 1)sodium d-γ-tocopherol phosphate 10.0 2) sodium ascorbyl 2-phosphate 10.03) glycerol 20.0 4) octyldodecyl myristate 60.0

EFFECT OF THE INVENTION

The skin whitening external preparations contain the tocopherolphosphate and/or the salt thereof as an active ingredient capable ofprevention and/or removal of skin pigmentation. The externalpreparations have excellent skin whitening effects and are readilyproducible so that they can find wide use for the purpose of skinwhitening.

Also, the cosmetics comprising the above skin whitening externalpreparations may be effectively employed in variety of forms, such asgels, emulsions and liquids, particularly lotions, emulsions, gels andcosmetic liquids.

The cosmetic cares using any of the above skin whitening externalpreparations and cosmetics are effective for prevention and/or removalof skin pigmentation.

1. A skin whitening external preparation which comprises tocopherolphosphate and/or a salt thereof as an active ingredient capable ofprevention and/or removal of skin pigmentation.
 2. The skin whiteningexternal preparation of claim 1, wherein the tocopherol phosphate isrepresented by the formula (1):

wherein R₁, R₂ and R₃ are each hydrogen or a methyl group.
 3. The skinwhitening external preparation of claim 1, wherein the tocopherolphosphate is α-tocopherol phosphate.
 4. The skin whitening externalpreparation of claim 3, wherein the α-tocopherol phosphate isdl-α-tocopherol phosphate.
 5. The skin whitening external preparation ofclaim 3, wherein the α-tocopherol phosphate is d-α-tocopherol phosphate.6. The skin whitening external preparation of claim 2, wherein thetocopherol phosphate is γ-tocopherol phosphate.
 7. The skin whiteningexternal preparation of claim 6, wherein the γ-tocopherol phosphate isd-γ-tocopherol phosphate.
 8. The skin whitening external preparation ofclaim 2, wherein the tocopherol phosphate is δ-tocopherol phosphate. 9.The skin whitening external preparation of claim 8, wherein theδ-tocopherol phosphate is d-δ-tocopherol phosphate.
 10. The skinwhitening external preparation of any of claims 1 to 9, wherein the saltof tocopherol phosphate is a sodium salt.
 11. The skin whiteningexternal preparation of any of claims 1 to 9, wherein the content of thetocopherol phosphate and/or the salt thereof is from 0.1 to 10% by mass.12. A cosmetic comprising the skin whitening external preparation of anyof claims 1 to
 9. 13. The cosmetic of claim 12, which is in the form ofa gel, emulsion or lotion.
 14. A cosmetic care using the cosmetic ofclaim
 12. 15. A method of using tocopherol phosphate and/or a saltthereof comprising preparing skin whitening external preparationscontaining tocopherol phosphate and/or a salt thereof as an activeingredient capable of prevention and/or removal of skin pigmentation.16. A skin whitening method comprising percutaneously administratingtocopherol phosphate and/or a salt thereof.